南京中医药大学学报2025,Vol.41Issue(3):352-362,11.DOI:10.14148/j.issn.1672-0482.2025.0352
疏肝益肾方对乳腺癌肺转移微环境基因表达谱及免疫相关基因表达的影响
Effect of Shugan Yishen Recipe on Microenvironment Gene Expression Profile and Immune-Related Gene Expression in Lung Metastasis of Breast Cancer
摘要
Abstract
OBJECTIVE To investigate the mechanism of inhibition of breast cancer lung metastasis by Shugan Yishen Recipe by studying the effects of Shugan Yishen Recipe(SGYSR)on gene expression in the lung microenvironment of mice with breast cancer.METHODS A high metastasis model of breast cancer was constructed,and the mice were randomly divided into saline group,low,medium,high(0.5,1,2 g·kg-1)Shugan Yishen Recipe groups,and docetaxel group(5 mg·kg-1),and intervened for 28 days.HE staining was used to observe the lung tissue structure;transcriptome analysis was performed on the metastatic foci,and the key differential gene expression was screened by bioinformatics analysis of the GO and KEGG pathway characteristics of the gene ex-pression profiles,and the expression of key immune genes was analyzed by qPCR and Western blot.The expression of MDSCs was de-tected by flow cytometry;the expression of cytokines and chemokines including Cxcl2,and GM-CSF was detected by ELISA.RE-SULTS Compared with the saline group,the number of metastatic nodules in lung tissues of the middle and high dose groups of Shu-gan Yishen Recipe and docetaxel group were correspondingly lower;HE staining suggested that the degree of lung pathology was im-proved.There were 814 differentially expressed genes in the lung microenvironment of the high-dose group of Shugan Yishen Recipe and the saline group,of which 713 genes were down-regulated and 101 genes were up-regulated;screening for key inflammatory medi-ator genes in the Shugan Yishen Recipe group,Nfkbiz,Tnfaip3,Maff,Hspa1a,Hspb1 and Cxcl2,the inflammatory genes in the Shu-gan Yishen Recipe,as compared with that of the saline group,were significantly down-regulated(P<0.05,P<0.01),and ultimately its results were consistent with the trend of the transcriptome results.Western blot was used to verify the results at the protein level,and it was found that compared with the saline group,the protein expression levels of Nfkbiz,Tnfaip3,Maff,Hspa1a and Cxcl2 in the Shugan Yishen Recipe group were decreased(P<0.05,P<0.01),while the protein expression of Hspb1 was up-regulated(P<0.01).Both the Shugan Yishen Recipe group and the docetaxel group could inhibit the expression of MDSCs(P<0.001),and the ex-pression of Cxcl2,and GM-CSF decreased to a certain extent(P<0.05,P<0.01).CONCLUSION Shugan Yishen Recipe can in-hibit breast cancer lung metastasis and regulate the lung immune microenvironment genes in a wide range.关键词
乳腺癌/肺部微环境/基因表达谱/炎性介质/疏肝益肾方Key words
breast cancer/lung microenvironment/gene expression profiling/inflammatory mediator/Shugan Yishen Recipe分类
医药卫生引用本文复制引用
李心怡,崔闯,陈皖晴,朱为康..疏肝益肾方对乳腺癌肺转移微环境基因表达谱及免疫相关基因表达的影响[J].南京中医药大学学报,2025,41(3):352-362,11.基金项目
上海市"科技创新行动计划"医学创新研究专项项目(20Y21902600) (20Y21902600)
上海医学创新发展基金会"未来计划"项目(WL-LXBB-2021002K,WL-HBMS-2022008K,WL-QNRC-2022001K) (WL-LXBB-2021002K,WL-HBMS-2022008K,WL-QNRC-2022001K)
免疫与炎症全国重点实验室开放课题项目(2024Q0010) (2024Q0010)